The Peyer's Patch follicle associated epithelium (FAE) provides both an epithelial barrier over mucosal lymphoid tissue and specialized delivery of antigens to the immune system. Although the best-known function of the FAE is the transcytosis mediated by M cells, the differentiation and function of FAE must be considered as a whole. Indeed, the FAE should be viewed as a complex tissue, with several functional subsets, and direct interactions with embedded lymphocytes and underlying immune tissue. We have identified several FAE associated genes that may encode specialized receptors for transcytosis of antigens to underlying lymphoid tissue. Some of these receptors may also signal adjuvant activity for mucosal immunity. Our working hypothesis is that the FAE functions as a filter for molecules gaining access to the Peyer's Patch, and as an innate immune sensor. Consistent with this notion, expression of some genes among cells of the FAE appears to mark distinct functional subsets. We propose a study of FAE using both in vitro and in vivo models, to reveal the relationships among FAE subsets in vivo with respect to their developmental biology and function. Three specific aims are proposed: Specific aim 1. How are FAE phenotypic subsets related? ; Specific aim 2. How does sub-cellular reorganization occur during differentiation of FAE and M cell phenotypes? ; Specific aim 3. Do M cells differentiate from committed precursors or common FAE enterocytes? Information gained from the proposed studies will help the understanding of pathogenesis mechanisms of intestinal infectious diseases, and provide important targets in the design of mucosal vaccines.